Affiliations: Department of Medical Engineering and Systems Cardiology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan | Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan
Abstract: Rho-kinase modulates calcium sensitivity of the myosin light chain in smooth muscle cells and has been implicated as playing a pathogenetic role in cardiovascular disorders. This paper was aimed to determine whether hydroxyfasudil (a specific Rho-kinase inhibitor) exerts cardioprotective effect on coronary ischemia–reperfusion (I/R) injury, and if so, whether NO is involved. Canine subepicardial small arteries (diameter≥100 μm) and arterioles (diameter<100 μm) were observed by a CCD intravital microscope during coronary I/R. Coronary vascular responses to endothelium-dependent (acetylcholine) and -independent (papaverine) vasodilators were examined after I/R under three conditions: control, preconditioning, and hydroxyfasudil. Coronary I/R significantly impaired coronary vasodilation to acetylcholine, whereas hydroxyfasudil completely preserved the responses, as did preconditioning. Hydroxyfasudil also significantly reduced myocardial infarct size. These results indicated that hydroxyfasudil exerts cardioprotective effects on coronary I/R injury in vivo, for which NO-mediated mechanism may be involved.
